BIDMC Drug – Drug Interactions

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Generic Drug Name or Category / Interacts With /

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ACE INHIBITORS
BENAZEPRILCAPTOPRIL
ENALAPRIL MALEATE
ENALAPRILAT
LISINOPRIL
MOEXIPRIL
QUINAPRIL
RAMIPRIL
TRANDOLAPRIL / K-SPARING DIURETICS
AMILORIDE
SPIRONOLACTONE
TRIAMTERENE / 1B / Diuretics and ACE inhibitors used together may cause hypotension. The combination of ACE inhibitors and potassium-sparing diuretics may cause significant hyperkalemia. This effect is particularly significant in patients with renal insufficiency.
ACE INHIBITORS
BENAZEPRILCAPTOPRIL
ENALAPRIL MALEATE
ENALAPRILAT
LISINOPRIL
MOEXIPRIL
QUINAPRIL
RAMIPRIL
TRANDOLAPRIL / POTASSIUM
POTASSIUM ACETATE
POTASSIUM BICARBONATE/CIT AC
POTASSIUM CHLORIDE
POTASSIUM IODIDE
POTASSIUM PHOS,M-BASIC-D-BASIC / 1A / ACE inhibitors may decrease aldosterone causing hyperkalemia. When ACE inhibitors are coadministered with potassium-containing products, the risk of hyperkalemia is increased.
ALLOPURINOL / AZATHIOPRINE / 1A / Allopurinol inhibits the metabolism of oral azathioprine, increasing serum azathioprine levels. Concomitant use can cause marked bone marrow suppression. If these drugs must be used together, azathioprine oral doses should be reduced to 25-30% of the usual dosage and the patient should be monitored closely for toxicity. Intravenous azathioprine does not appear to be affected by allopurinol.
ALLOPURINOL / THEOPHYLLINE / 1B / Concurrent use of allopurinol and theophylline may result in theophylline toxicity (nausea, vomiting, palpitations, seizures). This interaction is more likely to occur with daily allopurinol doses of 600 mg or more.
AMIODARONE / CYCLOSPORINE / 1B / Reports suggest that amiodarone may interfere with the clearance of cyclosporine. The risk of cyclosporine toxicity may increase.
AMIODARONE / DIGOXIN / 1A / Amiodarone may increase serum digoxin concentrations by up to 100%. Amiodarone may increase intestinal transit time, reduce renal clearance of digoxin, inhibit hepatic metabolism of digoxin, displace digoxin from protein-binding sites, and, in some cases, induce hypothyroidism. Empirical reduction or discontinuation of digoxin should be considered. Management also consists of monitoring clinical response or checking serum digoxin levels if toxicity is suspected.
AMIODARONE / WARFARIN / 1A / Amiodarone may inhibit hepatic metabolism of warfarin. A 30% to 50% reduction in warfarin dosage is recommended, as is frequent monitoring of INR.
AZOLE ANTIFUNGALS
CLOTRIMAZOLEFLUCONAZOLE
ITRACONAZOLE
KETOCONAZOLE
MICONAZOLE /

CYCLOSPORINE

/ 1B / Some azoles, particulary Ketoconazole and Itraconazole, may inhibit the hepatic metabolism of cyclosporine. Serum cyclosporine concentrations and nephrotoxicity may increase fourfold. Cyclosporine dosage reductions of 80% have been necessary in some patients.
AZOLE ANTIFUNGALS
CLOTRIMAZOLEFLUCONAZOLE
ITRACONAZOLE
KETOCONAZOLE
MICONAZOLE / HMG COA REDUCTASE INHIBITORS
ATORVASTATIN
CERIVASTATIN
FLUVASTATIN
LOVASTATIN
PRAVASTATIN
SIMVASTATIN / 1B / The use of HMG-CoA reductase inhibitors during azole therapy may increase CK, AST, ALT, and LDH serum levels.
BETA BLOCKERS
ACEBUTOLOLATENOLOL
BETAXOLOL
BISOPROLOL FUMARATE
CARVEDILOL
ESMOLOL
LABETALOL
METOPROLOL
NADOLOL
PINDOLOL
PROPRANOLOL
SOTALOL
TIMOLOL / AMIODARONE / 1A / The combination of these drugs may cause severe bradycardia, cardiac arrest, or ventricular fibrillation. Use extreme caution using these drugs together.
CALCIUM CHANNEL BLOCKERS
AMLODIPINE BESYLATEDILTIAZEM
FELODIPINE
ISRADIPINE
NICARDIPINE
NIFEDIPINE
NISOLDIPINE
VERAPAMIL / BETA BLOCKERS
ACEBUTOLOLATENOLOL
BETAXOLOL
BISOPROLOL FUMARATE
CARVEDILOL
ESMOLOL
LABETALOL
METOPROLOL
NADOLOL
PINDOLOL
PROPRANOLOL
SOTALOL
TIMOLOL / 1B / The concomitant use of calcium channel blockers and beta-blockers can occasionally cause AV heart block and left-ventricular dysfunction.
CALCIUM CHANNEL BLOCKERS
AMLODIPINE BESYLATEDILTIAZEM
FELODIPINE
ISRADIPINE
NICARDIPINE
NIFEDIPINE
NISOLDIPINE
VERAPAMIL / RITONAVIR / 1B / Ritonavir may significantly increase levels of calcium channel blockers. Be careful using this combination of drugs, and monitor for toxicity.
CIMETIDINE / WARFARIN / 1A / Cimetidine inhibits the hepatic metabolism of warfarin, and may increase its anticoagulant effect over a one to two week period. If given together, the INR should be monitored, and the lowest possible dose of cimetidine should be used. Another histamine-2 antagonist may be used with less risk of interaction.
CLOPIDOGREL BISULFATE /

NSAIDs

IBUPROFEN
INDOMETHACIN
KETOROLAC TROMETHAMINE
NAPROXEN
PIROXICAM / 1B / The coadministration of nonsteroidal antiinflammatory drugs (NSAIDs) and clopidogrel should be undertaken with extreme caution. The coadministration of clopidogrel with naproxen resulted in occult gastrointestinal blood loss in healthy volunteers. The mechanism may be due to additive platelet inhibition. Additionally, diclofenac, ibuprofen, naproxen, mefenamic acid, indomethacin and piroxicam are substrates for the cytochrome P450 isoenzyme 2C9 inhibited by clopidogrel. The clinical magnitude of this interaction is not known. The clinician should observe the patient for increased NSAID toxicity if these agents are co-administered with clopidogrel.
CYCLOSPORINE / MACROLIDES
AZITHROMYCIN CLARITHROMYCINDIRITHROMYCIN ERYHTROMYCIN BASEERYTHROMYCIN ESTOLATE
ERYTHROMYCIN ETHYLSUCCINATE
ERYTHROMYCIN GLUCEPTATE
ERYTHROMYCIN LACTOBIONATE
ERYTHROMYCIN STEARATE
TROLEANDOMYCIN / 1B / Some macrolide antibiotics may significantly increase cyclosporine serum concentrations, possibly by inhibiting hepatic metabolism of cyclosporine, resulting in nephrotoxicity. Appropriate monitoring of cyclosporine serum concentrations during co-administration is recommended.
CYCLOSPORINE / FOSCARNET SODIUM / 1B / Foscarnet and cyclosporine used together may increase the risk of nephrotoxicity and renal failure. If these agents are used concomitantly, consider close observation of renal function and discontinue foscarnet if needed.
CYCLOSPORINE / GEMFIBROZIL / 1B / Cyclosporine used concurrently with high doses of Gemfibrozil can cause rhabdomyolysis.
CYCLOSPORINE / HMG COA REDUCTASE INHIBITORS
ATORVASTATIN
CERIVASTATIN
FLUVASTATIN
LOVASTATIN
PRAVASTATIN
SIMVASTATIN / 1B / Cyclosporine used concurrently with moderate to high doses of HMG CoA reductase inhibitors can cause rhabdomyolysis.
CYCLOSPORINE / VERAPAMIL
DILTIAZEM / 1A / Verapamil and Diltiazem may inhibit the hepatic metabolism of cyclosporine causing increased trough and steady state levels, and the risk of nephrotoxicity. Cyclosporine levels should be monitored, and dosage should be adjusted as needed.
DAPSONE / SAQUINAVIR / 1A / Saquinavir may competitively inhibit the metabolism of drugs that are substrates of the cytochrome P-450 (3A4) microsomal enzymatic pathway. Plasma levels of these drugs may be elevated. The patient should be monitored closely for toxicities and lower dosages of these drugs may be necessary
DIGOXIN / MACROLIDES
AZITHROMYCIN CLARITHROMYCINDIRITHROMYCIN ERYHTROMYCIN BASEERYTHROMYCIN ESTOLATE
ERYTHROMYCIN ETHYLSUCCINATE
ERYTHROMYCIN GLUCEPTATE
ERYTHROMYCIN LACTOBIONATE
ERYTHROMYCIN STEARATE
TROLEANDOMYCIN / 1A / Theoretically this interaction might occur with other macrolides. Patients should be closely monitored for evidence of digoxin toxicity if macrolide antibiotics and digoxin must be coadministered.
DIGOXIN / ITRACONAZOLE / 1B / The addition of itraconazole to patients stabilized on digoxin has resulted in two to fourfold increases in serum digoxin concentrations and digoxin toxicity. The mechanism is unknown. The onset of toxicity generally occurs within 9 to 13 days after the start of itraconazole therapy.
DIGOXIN / QUINIDINE / 1A / Quinidine significantly increases serum digoxin levels in more than 90% of patients. The mechanism is related to reduced renal and biliary clearance, and reduced volume of digoxin distribution. Empiric reduction in digoxin dosing may be considered at the initiation of combination therapy. Modifications in dosage should be expected.
DIGOXIN / TETRACYCLINE / 1A / Tetracyclines may increase serum levels of orally administered digoxin in about 10% of the population. The mechanism may be related to changes in intestinal flora that alter the absorption of digoxin. If these drugs must be used together, the patient should be closely monitored for digoxin toxicity.
DIGOXIN / VERAPAMIL / 1A / Verapamil increases digoxin levels significantly in most patients. This important and possibly severe interaction is related to several complex mechanisms. Digoxin and verapamil have additive effects in slowing AV conduction. Verapamil also decreases the elimination of digoxin. If verapamil and digoxin are used together to control a supraventricular tachyarrhythmia, the dosage of each drug may have to be reduced.
EFAVIRENZ / CLARITHROMYCIN / 1B / Efavirenz increases the metabolism of clarithromycin. No dosage adjustment is recommended when these drugs are co-administered, but a rash occurs in 46% of patients administered clarithromycin and efavirenz concomitantly. Alternative therapy such as azithromycin might be considered.
EFAVIRENZ / INDINAVIR SULFATE / 1B / Coadministration of efavirenz and indinavir causes a decreased indinavir level. The mechanism of this interaction is hepatic enzyme induction of CYP3A4 by efavirenz. The dosage of indinavir should be increased from 800 mg every 8 hours to 1000 mg every 8 hours when these drugs are administered concomitantly.
ENOXAPARIN
DALTEPARIN
TINZAPARIN / HEPARIN / 1A / Dalteparin may increase the risk of bleeding from heparin. The mechanism is additive inhibition of thrombin and factor Xa. If these agents must be used together, extreme caution is advised, and the patient should be monitored for signs of bleeding. Other low-molecular-weight heparins (LMWHs) may interact with heparin in a similar manner.
KETOROLAC /

NSAIDs

IBUPROFEN
INDOMETHACIN
KETOROLAC TROMETHAMINE
NAPROXEN
PIROXICAM / 1B / Ketorolac is contraindicated in patients concurrently receiving aspirin or NSAIDs because of the cumulative risks of inducing serious NSAID-related adverse events (peptic ulcers, gastrointestinal bleeding and/or perforation).
MACROLIDES
AZITHROMYCIN CLARITHROMYCINDIRITHROMYCIN ERYHTROMYCIN BASEERYTHROMYCIN ESTOLATE
ERYTHROMYCIN ETHYLSUCCINATE
ERYTHROMYCIN GLUCEPTATE
ERYTHROMYCIN LACTOBIONATE
ERYTHROMYCIN STEARATE
TROLEANDOMYCIN / HMG COA REDUCTASE INHIBITORS
ATORVASTATIN
CERIVASTATIN
FLUVASTATIN
LOVASTATIN
PRAVASTATIN
SIMVASTATIN / 1B / When lovastatin and some macrolide antibiotics (erythromycin) have been used concomitantly in severely ill patients, severe myopathy and rhabdomyolysis have resulted. The mechanism appears to be inhibition of lovastatin metabolism by the macrolide. Patients should be instructed to report symptoms of muscle pain, weakness, or tenderness. If symptoms occur, creatine kinase should be measured. If creatine kinase is elevated, the drugs should be discontinued. A similar reaction may occur with other HMG-CoA reductase inhibitors.
FENTANYL / RITONAVIR / 1A / Ritonavir may significantly increase fentanyl plasma levels. Patients should be closely observed for toxicity if these drugs are used together.
GEMFIBROZIL / HMG COA REDUCTASE INHIBITORS
ATORVASTATIN
CERIVASTATIN
FLUVASTATIN
LOVASTATIN
PRAVASTATIN
SIMVASTATIN / 1B / Gemfibrozil and lovastatin used together can cause severe myopathy and rhabdomyolysis. Combined use of gemfibrozil or clofibrate with other HMG-CoA reductase inhibitors may increase the risk of this side effect as well. If this combination must be used, the patient should be instructed to report symptoms of muscular pain, weakness, or tenderness. If creatine kinase is elevated, the drugs should be discontinued.
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / MEPERIDINE / 1A / Immediate onset of excitement, sweating, rigidity, and hypertension can occur when monoamine oxidase inhibitors (MAOIs) are used concurrently with meperidine. Death has been reported. Similar effects have been reported with propoxyphene and fentanyl, but not with other analgesics. The combination of narcotic analgesics and MAOIs should be avoided if possible. An MAOI plus meperidine should not be used under any circumstances.
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / COMT INHIBITORS
ENTACAPONE
LEVODOPA
TOLCAPONE / 1B / Monoamine oxidase inhibitors (MAOIs) stop the catalyst enzyme catechol-O-methyltransferase (COMT) from metabolizing levodopa to 3-O-methyldopa in the periphery, and in the brain.
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / SSRI ANTIDEPRESSANTS
CITALOPRAM
FLUOXETINE
FLUVAOXAMINE MALEATE
PAROXETINE
SERTRALINE / 1A / Severe and sometimes fatal reactions involving elevations in blood pressure, hyperthermia, rigidity, and autonomic instability have occurred in patients taking SSRIs in combination with monoamine oxidase inhibitors (MAOIs). A minimum period of two weeks should separate use of these drugs.
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / SYMPATHOMIMETIC AGENTS
DOBUTAMINE
DOPAMINE
EPHEDRINE
EPINEPHRINE
ISOPROTERENOL
MIDODRINE
NOREPINEPHRINE
PHENYLEPHRINE
PSEUDOEPHEDRINE
TERBUTALINE / 1B / Sympathomimetic amines used with monoamine oxidase inhibitors may precipitate severe hypertensive reactions
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / TRICYCLIC ANTIDEPRESSANTS
AMITRIPTYLINE
AMOXAPINE
CLOMIPRAMINE
DESIPRAMINE
DOXEPIN
IMIPRAMINE
NORTRIPTYLINE
PROTRIPTYLINE
TRIMIPRAMINE MALEATE / 1B / Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants when used together may cause hyperpyretic crises, disseminated intravascular coagulation, convulsions, and death. The mechanism is unknown. Although these agents have been used together safely in many patients, some investigators recommend that tricyclic antidepressants not be used within two weeks of MAOIs.
MAO INHIBITORS
ISOCARBOXAZIDPHENELZINE
SELEGELINE
TRANYLCYPROMINE / VENLAFAXINE / 1A / Monoamine oxidase inhibitors (MAOIs) used together with anti-depressants may cause severe, even fatal, reactions. The reactions reported with the newer antidepressants include hyperthermia, rigidity, myoclonus, autonomic instability, and mental status changes that range from delirium to coma. In general, MAOIs and venlafaxine or other SSRIs should be separated by 2 weeks.
NARCOTICS
CODEINE
FENTANYL
HYDROMORPHONE
MEPERIDINE
METHADONE
MORPHINE
OXYCODONE
OXYMORPHONE
PROPOXYPHENE / BENZODIAZEPINES
ALPRAZOLAM
CHLORDIAZEPOXIDE
CLONAZEPAM
CLORAZEPATE DIPOTASSIUM
DIAZEPAM
FLURAZEPAM
LORAZEPAM
MIDAZOLAM
OXAZEPAM
TEMAZEPAM
TRIAZOLAM / 1B / Narcotics and benzodiazepines used together can cause excessive respiratory and CNS depression. The mechanism may be related in part to inhibition of hepatic oxidation of the benzodiazepine. Alprazolam has been most implicated in this interaction. Such interactions are more likely to occur in the benzodiazepine and narcotic “naive” patient.
NEVIRAPINE / PROTEASE INHIBITORS
AMPRENAVIR
INDINAVIR
MIGLITOL
RITONAVIR
SAQUINAVIR / 1B / Because nevirapine may induce the hepatic P450 cytochrome system, reductions in plasma concentrations of protease inhibitors theoretically may occur. The manufacturer recommends that, until clinical studies provide information on dosage adjustments, protease inhibitors should not be administered concomitantly with nevirapine.
NIACIN / HMG COA REDUCTASE INHIBITORS
ATORVASTATIN
CERIVASTATIN
FLUVASTATIN
LOVASTATIN
PRAVASTATIN
SIMVASTATIN / 1B / Lovastatin and niacin used together may cause severe myopathy and rhabdomyolysis. Although this reaction has not been reported with concomitant use of pravastatin and niacin, patients should be instructed to report symptoms of muscle pain, weakness, or tenderness. If creatine kinase is elevated, the drugs should be discontinued.

NM BLOCKERS

ATRACURIUM BESYLATECISATRACURIUM BESYLATEDOXACURIUM CHLORIDE
MIVACURIUM CHLORIDE
PANCURONIUM BROMIDE
PIPECURONIUM BROMIDE
RAPACURONIUM BROMIDE
ROCURONIUM BROMIDE
SUCCINYLCHOLINE CHLORIDE
TUBOCURARINE CHLORIDE
VECURONIUM BROMIDE /

AMINOGLYCOSIDES

AMIKACIN
GENTAMICIN